Atlantic conjunctures in Anglo-American neurology: Lewis H. Weed and Johns Hopkins neurology, 1917-1942

The emergence of neurology at Johns Hopkins presents a case study for reconsidering the international and institutional contexts of neurology generally. Using a variety of sources, Hopkins's interwar plans for neurology are presented and contextualized in the international environment of neurology, medical research, and philanthropy. During this period, neurology across the world, especially in Britain, was undergoing vast institutional changes. In order for Hopkins to remain at the forefront of excellence in both medicine and medical education, a program in neurology was deemed essential, and this would seem now to have been an unproblematic advance. Spearheading the project for the establishment of neurology at Hopkins was the dean of the medical school, Lewis H. Weed. Weed attempted from 1919 until 1942 to establish a department of neurology but had only limited success. The fact that finding support proved challenging for Weed and Johns Hopkins casts a provocative light on the broader historiography of neurology and illustrates the important role of the international context in defining neurology professionally.     

Electronegative electroretinogram associated with topiramate toxicity and vitelliform maculopathy

Topiramate is known to cause ocular side effects such as refractive changes and angle closure. We describe a patient with an electronegative electroretinogram (ERG) which may have been related to topiramate use. Electronegative ERG’s have been associated with other drugs in humans as well as topiramate use in rabbits. However, this would be the first suggestion of causality in humans.     

Influence of ovariectomy and masticatory hypofunction on mandibular bone remodeling

Introduction:  This study was designed to examine the effect of masticatory hypofunction and estrogen deficiency on mandible bone mass and compare this site with spine and femoral bone.
Methods:  Twenty-four rats were ovariectomized (OVX) or Sham-operated (Sham) and analyzed after feeding with hard diet (Hard) or soft diet (Soft). They were divided into four groups: (GI)Sham-Hard; (GII)OVX-Hard; (GIII)Sham-Soft and (GIV)OVX-Soft. Bone mineral density (BMD) was measured in the spine and femur in the baseline and at the end of the study, and ΔBMD (final BMD − baseline BMD) was calculated. In mandible bone, BMD and histomorphometry were analyzed at the end of the experiment.
Results:  Sham rats showed higher spine (GI: 13.5% vs GII: 0.74%, P  <   0.01; GIII: 10.67% vs GIV: −4.36%, P  <   0.001) and femur ΔBMD (GI: 14.43% vs GII: 4.42%, P  <   0.01; GIII: 10.58% vs GIV: 0.49%, P  <   0.001) than OVX, but no difference was observed in mandible BMD among these groups ( P  >   0.05). Soft-diet groups showed decreased mandible BMD compared with hard-diet groups (GIV vs GII, P  <   0.01; GIII vs GI, P  <   0.01). Similarly, mandibular condyle histomorphometry showed that soft-diet groups presented a significant decrease in trabecular thickness and volume (GIV vs GII, P  <   0.05; GIII vs GI, P  <   0.01) compared with hard diet.
Conclusion:  Our results suggest that mandibular bone loss resulted from decreased of mechanical loading during mastication, and was not affect by estrogen depletion.     

Higher Plasma Soluble Receptor for Advanced Glycation End Products (sRAGE) Levels Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes: A 12-Year Follow-Up Study

OBJECTIVE

To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunction, low-grade inflammation, arterial stiffness, and advanced glycation end products (AGEs).

RESEARCH DESIGN AND METHODS

We prospectively followed 169 individuals with diabetic nephropathy and 170 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of sRAGE and other biomarkers were measured at baseline. The median follow-up duration was 12.3 years (7.6–12.5).

RESULTS

The incidence of fatal and nonfatal CVD and all-cause mortality increased with higher baseline levels of log-transformed sRAGE (Ln-sRAGE) independently of other CVD risk factors: hazard ratio (HR) 1.90 (95% CI 1.13–3.21) and 2.12 (1.26–3.57) per 1-unit increase in Ln-sRAGE, respectively. Adjustments for estimated glomerular filtration rate (eGFR_MDRD), but not or to a smaller extent for markers of endothelial dysfunction, low-grade inflammation, arterial stiffness, and AGEs, attenuated these associations to HR 1.59 (95% CI 0.91–2.77) for fatal and nonfatal CVD events and to 1.90 (1.09–3.31) for all-cause mortality. In addition, in patients with nephropathy, the rate of decline of GFR was 1.38 ml/min/1.73 m² per year greater per 1-unit increase of Ln-sRAGE at baseline (P = 0.036).

CONCLUSIONS

Higher levels of sRAGE are associated with incident fatal and nonfatal CVD and all-cause mortality in individuals with type 1 diabetes. sRAGE-associated renal dysfunction may partially explain this association.Recent studies have suggested a potential role of the receptor for advanced glycation end products (RAGE) in the development of vascular disease in individuals with diabetes (1). At the molecular level, RAGE is upregulated in atherosclerotic lesions in diabetes (2). RAGE-induced production of adhesion molecules (3–5) and inflammatory cytokines (4) could contribute to endothelial (4,5) and renal dysfunction (6), low-grade inflammation (4,5), and arterial stiffening, all of which may partially explain the increased cardiovascular disease (CVD) in diabetes.We have recently shown, in a large cross-sectional study of type 1 diabetes (EURODIAB), that plasma levels of sRAGE were positively associated with macro- and microvascular complications, and also with endothelial and renal dysfunction, and low-grade inflammation as pathophysiological mechanisms that explained in part the associations of sRAGE with vascular complications (7). Whether sRAGE is associated with incident fatal and nonfatal CVD as well as all-cause mortality in individuals with type 1 diabetes has never been investigated. In addition, the extent to which any such associations could be explained by markers of endothelial and renal dysfunction, low-grade inflammation, arterial stiffness, and AGEs is also not known. We hereby address these questions in a 12-year prospective follow-up study.